Finasteride, a synthetic 4-azasteroid compound, 4-azaandrost-1-ene-17-carboxamide, N-(1,1-dimethylethyl)-3oxo-(5alpha 17beta)-. The empirical formula is C23H36N2O2. Finasteride is sold under the trade name Proscar, as identified by U.S. Pat. No. 5,175,155, the entire disclossure is incorporated by reference herein, is known for use in treatment of prostatic carcinoma.
Bicalutamide, a non-steroidal anti-androgen, chemical name is propanamide, N-[14-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-(+xe2x88x92), sold under the trade name Casodex, as identified by U.S. Pat. No. 4,636,505, the entire disclosure is incorporated by reference herein, is known for use in treatment of prostatic carcinoma.
Flutamide, an acetanilid, nonsteroidal antiandrogen having the chemical name, 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl] propanamide, sold under the trade name Eulexin, as identified by U.S. Pat. Nos. 3,995,060, and 4,474,813, the entire disclosure of which are in corporarted by reference herein, Flutamide is known for use in treatment of prostatic carcinoma.
Nilutamide, a nonsteroidal, orally active, antiandrogen, having the chemical name 5,5-dimethyl 3-[4-nitro 3-(trifluoromethyl)phenyl] 2,4-IMIDAZOLIDINEDIONE, sold under the trade name Nilandron, as identified by U.S. Pat. No. 5,023,088, the entire disclosure is incorporated by reference herein, is known for usee in the treatment of prostatic carcinoma.
Goserelin Acetate, a synthetic decapeptide of LHRH or GnRH, chemical structure is pyro-Glu-His-Trp-Ser-Tyr-D-Ser(Bu)-Leu-Arg-Pro-Azgly-NH2 acetate [C59H84N18O14 (C2H4O2)x wherex=1 to 2.4] sold under the trade name Zoladex, as identified by U.S. Pat. No. 5,510,460, the entire disclosure is incorporated by reference herein, is known ifor the treatment of prostatic carcinoma.
Leuprolide acetate is a synthetic nonapeptide of naturally occurring gonadotropin-releasing hormone (GnRH or LHRH), the chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) sold under the trade name Lupron or Lupron Depot, as identified by U.S. Pat. No. 4,897,256, the entire disclosure is incorporated by reference herein, is known for use in treatment of prostatic carcinoma.
Abarelix is a synthetic LHRH antagonist, the chemical name is N-Acetyl-3-(2-naphthyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridyl)-D-alanyl-L-seryl-N-methyl-L-tyrosyl-D-asparaginyl-L-leucyl-N6-isopropyl-L-lysyl-L-prolyl-D-alanylamide, manufacturer Praecis Pharmaceuticals Inc, the entire disclosure is incorporated herein, is known for use in treatment of prostatic carcinoma.
The present invention involves the use of combinations of these drugs in the prevention and treatment of
1) atherosclerosis
2) coronary artery disease
3) stroke
4) peripheral vascular disease
Inhibition of testosterone metabolism is important in control of prostatic carcinoma and benign prostatic hypertrophy. We have observed a decrease in atherosclerosis and coronary artery heart disease in patients to whom inhibitors of testosterone metabolism have been administered. This effect has been demonstrated both in patients taking finasteride for benign prostatic hypertrophy and in patients taking several LHRH or GnRH inhibitors for prostatic carcinoma. We conclude that testosterone metabolism plays a role in the development of atherosclerosis and its complications including coronary artery disease, and that by blocking testosterone metabolism the disease was treated and/or prevented.
In the treatment of prostatic carcinoma it has been demonstrated that when using inhibitors of LHRH secretion (Leuprolide, Goserelin) that addition of various anti-androgens; Bicalutamide, Nilutamide, and Flutamide, result in a lower serum testosterone. In addition it has been shown that the use of Finasteride with oral anti-androgens (Bicalutamide, Nilutamide, Flutamide) can suppress testosterone metabolism and control prostatic carcinoma. Our invention involves the use of these combinations for a new use, treatment/prevention of atherosclerosis and its complications including coronary artery disease.
The data which leads us to conclude that suppression of testosterone metabolism can result in lower rates of atherosclerosis and its complications including coronary artery disease is presented below:
It was observed that patients to whom finasteride was being administered for treatment of benign prostatic hypertrophy seemed to have a lower incidence of atherosclerosis and heart disease.
Finasteride was being administered at a dosage of a single oral 5 mg tablet a day. This is the same tablet used in treatment of BPH as disclosed in U.S. Pat. No. 5,175,155 and such dosage applies in the present invention. However, use of a 2 mg or 10 mg oral tablet is contemplated.